Research Interest: My research project is focusing on the role of the protease activated receptor 2 (PAR-2) in the pathogenesis of multiple sclerosis (MS). It is the most common immune-mediated disorder affecting the central nervous system. MS is caused by autoimmune-mediated damage of myelin sheet surrounding neurons in the brain and spinal cord, resulting in their damage. Activation of coagulation and neuroinflammation are observed in both MS patients and in a mouse model of the disease (EAE – Experimental Autoimmune Encephalitis). It has been shown that inhibition of tissue factor (TF) or thrombin attenuates the severity of EAE (paralysis and neuroinflammation) but at the same may lead to bleeding complications. TF in complex with factor VII (FVII) not only initiates the activation of the extrinsic coagulation pathway but can also trigger the intracellular signaling via activation of PAR-2. Our preliminary data demonstrates that PAR-2 deficiency significantly reduces paralysis and neuroinflammation in EAE mice. The main goal of my project is to investigate the cellular source and molecular mechanisms by which TF:FVIIa:PAR-2 pathway contributes to the pathology of MS using the EAE model.
Fatima Trebak, PhD
Postdoctoral fellow, T32 Research Trainee
Pawlinski Lab
Department of Medicine, Hematology Division.